Approximately 4 million individuals with Type 1 diabetes are treated with insulin in the U.S. individual with diabetes are constantly challenged to measure their blood glucose and administer the appropriate insulin dose to achieve tight glucose control. Tight glucose control, achievable with intensive insulin therapy, dramatically reduces secondary complication of diabetes, but requires frequent painful blood samples and increases the risk of hypoglycemia. Thus, individuals with the disease have long awaited an automatic closed-loop system that would control their glucose without the need for constant intervention. In the present proposal, two closed-loop systems to achieve this goal are developed. Both systems use a long-term fully implantable glucose sensor. One of the systems links the sensor to a fully implantable intraperitoneal insulin pump; the second links the sensor to an external insulin delivery pump. It is anticipated that some patients may require the implantable pump and that others will want to have the option of which pump to use. The systems have a common goal - to emulate, as closely as possible; glucose control achieved in a healthy individual. To achieve this goal, a physiology-insulin-delivery algorithm is proposed that emulates B-cell responses to glucose observed in individuals with normal glucose tolerance. The B-cell response is optimally adjusted to overcome delays associated with intraperitoneal (fully implanted pump) or subcutaneous (external pump) insulin delivery. Digital filters are developed to optimally remove noise in the sensor signal. A method of tuning the system, consistent with the level of glucose tolerance achieved by the B-cell is developed. Performance and safety of each system is evaluated. If successful, the systems can be expected to revolutionize the treatment of diabetes by dramatically reducing the burden placed on individuals with type 1 diabetes, and by reducing the costs of treating hypoglycemia and secondary complications.